Acute Pancreatitis View Online At

Acute Pancreatitis View online at http://pier.acponline.org/physicians/diseases/d268/d268.html

Module Updated: 2013-09-12 CME Expiration: 2016-09-12

Author Jonathan S. Appelbaum, MD

Table of Contents 1. Prevention ...... 2 2. Diagnosis ...... 4 3. Consultation ...... 10 4. Hospitalization ...... 12 5. Therapy ...... 13 6. Patient Education ...... 20 7. Follow-up ...... 21 References ...... 22 Glossary...... 29 Tables ...... 31 Figures ...... 41

Quality Ratings: The preponderance of data supporting guidance statements are derived from: level 1 studies, which meet all of the evidence criteria for that study type; level 2 studies, which meet at least one of the evidence criteria for that study type; or level 3 studies, which meet none of the evidence criteria for that study type or are derived from expert opinion, commentary, or consensus. Study types and criteria are defined at http://smartmedicine.acponline.org/criteria.html Disclaimer: The information included herein should never be used as a substitute for clinical judgement and does not represent an official position of the American College of Physicians. Because all PIER modules are updated regularly, printed web pages or PDFs may rapidly become obsolete. Therefore, PIER users should compare the module updated date on the offical web site with any printout to ensure that the information is the most current available. CME Statement: The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing education for physicians. The American College of Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should claim only credit commensurate with the extent of their participation in the activity. Purpose: This activity has been developed for internists to facilitate the highest quality professional work in clinical applications, teaching, consultation, or research. Upon completion of the CME activity, participants should be able to demonstrate an increase in the skills and knowledge required to maintain competence, strengthen their habits of critical inquiry and balanced judgement, and to contribute to better patient care. Disclosures: Jonathan S. Appelbaum, MD, current author of this module, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Deborah Korenstein, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. Richard B. Lynn, MD, FACP, Co-Editor, PIER, has no financial relationships with pharmaceutical companies, biomedical device manufacturers, or health-care related organizations. PIER is copyrighted ©2013 by the American College of Physicians. 190 N. Independence Mall West, Philadelphia, PA 19106, USA.

Acute Pancreatitis

Top 1. Prevention Avoid substances or procedures that can cause acute pancreatitis.

1.1 Avoid alcohol, smoking, the use of medications associated with AP, and unnecessary ERCP. Recommendations • Prevent AP by avoiding:

Alcohol Smoking Medications associated with AP Unnecessary ERCP See table Medications Associated with Acute Pancreatitis. • Consider using nitroglycerin to prevent recurrence of pancreatitis in post-ERCP patients. • Consider using rectal indomethacin prophylactically for post-ERCP pancreatitis. Evidence • Alcohol is responsible for 15% to 30% of cases of AP in the U.S. (1). • The incidence of pancreatitis is surprisingly low in alcoholic patients. For 100 alcoholic patients, pancreatitis develops in only 5% (2). These data indicate that in addition to the amount of alcohol ingested, unknown factors affect a person's susceptibility to injury; the exact mechanism of injury is not fully understood. • In a cohort study, smokers had an increased risk for developing AP (hazard ratio of 2.5) (3). • Documentation of drug-induced pancreatitis is difficult because it requires the pancreatitis to develop while the patient is receiving a medication; there is recovery once the medication is withdrawn, and pancreatitis recurs when the drug is reintroduced. Very few drugs have been proven to cause AP according to these criteria (4; 5; 6; 7). • In well-designed, prospective studies, the risk for pancreatitis after ERCP has been reported to range from 5% to 20% (8; 9; 10). • In an attempt to find a noninvasive alternative to ERCP, many studies have evaluated the role of one particular diagnostic modality (CT, EUS, and MRCP) in imaging the pancreatobiliary system (11; 12; 13; 14; 15). Because the results of many techniques are technology or operator dependent, we still lack test-relevant management algorithms and generalizability (12; 16). • In a study of 100 patients with AP, sensitivity of EUS was similar to that of ERCP for choledocholithiasis (97%), and the overall accuracies were 98% and 96%, respectively. EUS had a sensitivity of 98% (17). • A meta-analysis of 5 clinical trials supported the use of nitroglycerin to prevent post-ERCP pancreatitis (18). • A multicenter randomized trial of 602 patients showed that post-ERCP pancreatitis developed in 16.9% of the controls and 9.2% treated with rectal indomethacin (100 mg) (P=0.005). The incidence of moderate-to-severe pancreatitis in the treated group was half that in the control group (P=0.03) (19). • Data from a randomized, double-blind trial in 220 patients comparing diclofenac suppository with placebo given after ERCP showed that diclofenac decreased the incidence of post-ERCP pancreatitis (20). The difference in incidence of post-ERCP pancreatitis between the diclofenac group (7 of 110) and the placebo group (17 of 110) barely reached statistical significance (P=0.049). • A randomized, controlled trial compared somatostatin, 250 µg iv bolus, given immediately after the diagnostic portion of therapeutic ERCP with placebo. The incidence of post-ERCP pancreatitis was 4.4% in the somatostatin group (n=135) and 13.3% in the placebo group (n=135; P=0.01) (21).

Acute Pancreatitis

• A large (n=1127) randomized, controlled trial found that gabexate and somatostatin were ineffective for the prevention of post-ERCP pancreatitis (22). • A multicenter, placebo-controlled, randomized clinical trial looked at the effect of octreotide administration in the prophylaxis of post-ERCP pancreatitis and hyperamylasemia. The incidence of AP was 2.42% (10 of 414 patients) in the octreotide group and 5.26% (22 of 418 patients) in the control group (P=0.46). The incidence of hyperamylasemia was 12.32% (51 of 414 patients) in the octreotide group and 17.46% (73 of 418 patients) in the control group (P=0.41) (23). Rationale • Alcohol is strongly associated with AP, although the exact amount of alcohol needed to cause AP is unknown. • Smoking is an independent risk factor for AP. • Some medications can cause AP. • ERCP is a well-established cause of AP; magnetic resonance cholangiopancreatography, endoscopic ultrasonography, and helical CT can provide noninvasive or minimally invasive imaging of the pancreatobiliary system with no significant risk to the patient. • EUS has high sensitivity and specificity to evaluate the pancreatobiliary system, especially for bile- duct stones in patients with AP, and is emerging as the test of choice for intermediate or low suspicion of choledocholithiasis to help determine the need for ERCP. Comments • Abdominal fat may be a risk factor for acute pancreatitis according to a cohort study evaluating waist circumference and pancreatitis. The RR was 2.37 for a waist circumference >105 cm. No association was seen between BMI and risk for AP (24).

Acute Pancreatitis

Top 2. Diagnosis Base the diagnosis of AP on the presence of clinical symptoms, biochemical evidence of pancreatic injury, and imaging abnormalities of the pancreas. 2.1 Obtain detailed history to establish the diagnosis and possible cause of AP. Recommendations • Ask about abdominal pain that:

Is experienced in the epigastrium or diffusely throughout the entire upper abdomen Reaches its peak from 30 minutes to a few hours Is moderate to severe and constant in character with little fluctuation Radiates to the back Is difficult to alleviate by change of position in bed; occasionally decreases when sitting or leaning forward • Ask about nausea and vomiting, and if pain does not subside after vomiting. • Ask about specific factors that suggest certain causes of AP, including: • Medications associated with AP • Disorders associated with AP • Recent trauma • Smoking • Alcohol use • Elevated triglyceride levels • Recent ERCP • Family history of AP • Ask about any previous episodes of AP. • See table Etiology of Acute Pancreatitis. • See table Medications Associated with Acute Pancreatitis. Evidence • Consensus. Rationale • Abdominal pain is the most common symptom of AP and occurs in 95% of patients. • Rarely, pain may be located in the lower abdomen and may reflect the spread of pancreatic exudation throughout the abdomen. • Characteristics of the pain can contribute in establishing the diagnosis of AP. • Vomiting occurs in 85% of patients with AP. Comments • In the rare patients with severe AP who do not have abdominal pain, the diagnosis may be missed entirely if biochemical markers of pancreatic injury are not sought. 2.2 Use detailed physical exam to help establish the diagnosis of AP and to determine its etiology and severity. Recommendations • Check for abdominal tenderness; peritoneal signs may be present. • Listen for bowel sounds, which may be decreased or absent. • Check for signs that suggest specific etiology:

Jaundice, which raises the suspicion for gallstone pancreatitis

Acute Pancreatitis

Eruptive xanthomas, which suggest high triglyceride level • Check for signs that help detect consequences:

Hypovolemia (when due to fluid sequestreation, this is associated with tachycardia and low blood pressure) Infection GI bleeding Grey-Turner sign (ecchymosis in the abdominal flanks) Palpable pseudocyst Purtscher retinopathy (unusual complication that involves sudden loss of vision; fundoscopic appearance is with cotton-wool spots and hemorrhages confined to an area limited by the optic disk and macula) Altered mental status (can be due to hypotension, electrolyte imbalance, hypoxemia, or alcohol withdrawal) • Check for signs that suggest alternative diagnoses:

Findings of acute abdomen, such as severe tenderness with rebound tenderness, absent bowel sounds, pulsatile mass High fever, melena, or hematemesis raises suspicion of emergent alternative diagnoses • Note that fever is reported in 60% of patients with AP. • See table Differential Diagnosis of Acute Pancreatitis. Evidence • Consensus. Rationale • A thorough physical examination can provide clues to help establish the diagnosis and specific etiology of AP, consequences of severe AP, and alternative causes of abdominal pain. 2.3 Obtain serum markers of pancreatic injury. Recommendations • Check serum amylase and lipase levels in all patients suspected of having AP. • Recognize other conditions in which serum amylase can be elevated. • See table Laboratory and Other Studies for Acute Pancreatitis. • See table Causes of Increased Amylase. Evidence • Serum lipase is more specific than serum amylase level as a marker of AP (25) because serum amylase level can be elevated in numerous clinical situations unrelated to AP. • Serum lipase activity may be increased in the absence of pancreatitis in four instances: patients with renal insufficiency (26), patients with intra-abdominal conditions that resemble AP (25), patients receiving heparin (heparin activates lipoprotein lipase), and patients with head trauma or intracranial mass (27). • Determining the sensitivity and specificity of amylase and lipase level in the diagnosis of AP is a formidable challenge. All studies to date that address the role of amylase and lipase in diagnosing AP suffer from lack of a sufficient diagnostic gold standard (28). Rationale • Serum amylase and lipase levels are elevated in 75% to 90% of patients with AP. Comments • The lipase level remains elevated longer than the amylase level. 2.4 Obtain imaging studies to assist in the diagnosis of AP, to look for an underlying etiology, to judge severity, and to exclude other disease processes.

Acute Pancreatitis

Recommendations • Obtain chest and flat and upright abdominal radiographs in every patient with significant abdominal pain. • Perform ultrasonography to evaluate the biliary tract. • Obtain an abdominal CT scan when the diagnosis of AP is in question and to stage the severity and determine the presence of complications of AP. • In particular, obtain a contrast-enhanced, thin-section, multidetector-row CT scan to detect necrosis 48 to 72 hours after admission. • Obtain an abdominal MRI if there are contraindications to intravenous contrast-enhanced CT. • See table Laboratory and Other Studies for Acute Pancreatitis. • See figure Pancreatic Necrosis. • See figure Acute Interstitial Pancreatitis. • See figure Acute and Chronic Pancreatitis. • See figure Autoimmune Pancreatitis. Evidence • Some nonspecific radiographic findings that can suggest the diagnosis of AP include sentinel loop (localized ileus, involving the jejunum), colon cutoff sign (isolated distention of the transverse colon), duodenal distention with air-fluid levels, and pleural effusion localized to the left thorax (29). • Abdominal ultrasonography is 95% sensitive for the presence of gallbladder stones and biliary ductal dilatation but it is much less reliable for direct visualization of bile-duct stones (30). • Pancreatic visualization is limited by intestinal gas in 40% of patients with AP (31). • CT is the test of choice to determine the presence of local complications and severity of pancreatitis (32). • The severity of pancreatitis can be graded by CT (33; 34; 35), and a CT severity index can be calculated. The higher the CT severity index, the worse the prognosis (33; 34). In a prospective study, the incidence of organ failure increased significantly with increase of the CT score (36). • There has been concern that the use of intravenous contrast media early during the course of AP might intensify pancreatic necrosis. Decreased pancreatic capillary flow rates have been seen in two animal studies (37; 38). One retrospective study found that patients who underwent contrast- enhanced CT had longer hospitalization than patients who did not (39). In a cohort analytic study, incidence of local and systemic complications was increased in patients with mild AP who underwent contrast-enhanced CT (40). • Nonenhanced MRI may be as effective as contrast-enhanced CT for the assessment of the severity of AP (41). • EUS is an effective diagnostic tool to evaluate for bile-duct stones (17), and it also helps in the diagnosis of underlying pancreatic neoplasms, cystic lesions, and pancreas divisum (42; 43). • A prospective study showed that radiologic scoring systems do not perform better than clinical scoring systems for prediciting severity in acute pancreatitis (44). Rationale • Abdominal and chest radiographs should be obtained in patients suspected of having AP to exclude intra-abdominal or intrathoracic processes that can mimic AP (e.g., bowel perforation or obstruction) and because some radiographic findings may raise the suspicion for AP. • Biliary pancreatitis is the most common cause of AP in the U.S., and abdominal ultrasonography is the best and most cost-effective noninvasive test for the presence of gallbladder stones. • CT scan can exclude conditions that present similarly to AP, confirm the diagnosis of AP by showing abnormal appearance of the pancreas, and grade the severity of AP by determining the presence or absence of local complications (necrosis, abscess, or pseudocyst). Comments • Because prospective human studies are not available, it is reasonable to reserve contrast-enhanced CT for patients with severe AP, smoldering AP, or suspected local septic complications.

Acute Pancreatitis

• MRI is more expensive than CT and should be reserved for patients with contraindications for CT. 2.5 Obtain comprehensive laboratory evaluation in all patients with AP. Recommendations • Obtain in all patients with AP:

CBC Electrolyte levels Calcium level Glucose level Triglyceride level Liver function tests PT/PTT BUN/creatinine levels Test for arterial hypoxemia (pulse oximetry in mild cases of AP and arterial blood gas in severe cases of AP) • See table Laboratory and Other Studies for Acute Pancreatitis. Evidence • Metabolic abnormalities are seen in 16% of patients with AP and in 28% and 52% of patients with interstitial, noninfected necrotizing and infected necrotizing AP, respectively. Hypocalcemia and hypoglycemia are negative prognostic factors in AP (45; 46). • Alteration of coagulation factors has been described which can present clinically as DIC in the severe forms of AP (47). • Mild hypertriglyceridemia, i.e., triglyceride levels up to 400 mg/dL, are not unusual and can be seen in up to 75% of patients with miscellaneous causes of AP (48). However, marked hypertriglyceridemia with values >400 mg/dL is seen in approximately 20% of patients, and in that setting, it is seen in patients having an antecedent disorder of lipoprotein metabolism. • In a diagnostic study of 68 patients, hypertransaminasemia, as determined in the first 24 hours after admission, was a useful predictor of biliary etiology in patients with AP (49). Rationale • Leukocytosis is frequently seen in AP and is a nonspecific marker of inflammation; however, it may also be a sign of infection. • Electrolyte levels need to be monitored and replaced as needed. • Elevation of liver-function test results suggests biliary pancreatitis. • Calcium level is commonly decreased in AP. • Hyperglycemia may be present in 50% to 75% of patients with moderate to severe forms of AP. • Hypertriglyceridemia may be the cause of AP or a consequence of it. • Syndrome of disseminated intravascular coagulation may be seen in severe AP. • Renal insufficiency is a frequent finding in AP. 2.6 Determine the severity of AP. Recommendations • Determine the severity of AP based on the Atlanta consensus by examining three areas:

Early prognostic signs; traditionally used are the Ranson criteria, which are evaluated on admission and during the initial 48 hours of observation Organ failure, which is the most important indicator of severity in AP, defined by the presence of: o Shock (systolic blood pressure <90 mm Hg)

o Pulmonary insufficiency (PaO2 <60 mm Hg) o Renal failure (creatinine level >2 mg/dL)

Acute Pancreatitis

o Gastrointestinal bleeding (>500 mL/24h) Local complications consisting of: o Pancreatic necrosis o Pseudocyst or abscess • Be aware that according to the Atlanta consensus:

Severe AP is associated with organ failure or local complications and is further characterized by three or more Ranson criteria Mild AP is associated with minimal organ dysfunction and an uneventful recovery, and it lacks the described features of severe AP • Consider determining APACHE II score and obtaining C-reactive protein levels. • Be aware that other bedside indices are available. • Be aware that predicting severity accurately is limited. • See table Ranson's Criteria. Evidence • In 1992, 40 international authorities from six medical disciplines and 15 countries met in Atlanta, Georgia, and achieved unanimous consensus on a series of definitions and a clinically based classification system for AP (50). • A meta-analysis evaluated the discriminant power of Ranson signs in the prediction of AP severity and outcome compared with clinical judgment (51). Nineteen studies (n=2728) for severity prediction and 10 (n=1513) for prognosis were included. The Ranson's signs show a poor predictive power for severity and outcome of AP and did not differ from that of clinical judgment. • The APACHE II score for severity of disease classification, which includes a variety of physiologic variables, age points, and chronic health points that can be measured at admission and daily, can be used in patients with severe pancreatitis (52; 53). • The BISAP score, a bedside index, identifies patients at risk for mortality and increased morbidity within 24 hours of presentation. It has not been compared with other indices (54). • A prospective cohort study compared four bedside scoring systems and found all to have similar prognostic efficacy in determining risk stratification of AP (55). • C-reactive protein is an acute-phase reactant. Plasma levels >150 mg/L within the first 72 hours of disease correlate with the presence of necrosis, with sensitivity and specificity that are both greater than 80%. Because the peak is generally 36 to 72 hours after admission, this test is not helpful at admission in assessing severity (56; 57; 58). Rationale • Prognosis, therapy decisions, and need for consultation are based on the severity of AP attack. Comments • The presence of both organ failure and infection doubles the relative risk for death (59). 2.7 Consider disease processes with presentations similar to AP or those that can cause AP in approaching the differential diagnosis. Recommendations • Use history, physical examination, and laboratory studies to establish the diagnosis and the cause of AP. • See table Differential Diagnosis of Acute Pancreatitis. • See table Etiology of Acute Pancreatitis. Evidence • Consensus. Rationale • The differential diagnosis of AP is extensive.

Acute Pancreatitis

• Numerous conditions can cause AP but the two most common ones are alcohol and biliary stones. 2.8 Recognize that a cystic lesion in the pancreas may be due to AP (pseudocyst) or to cystic neoplasm of the pancreas. Recommendations • Consider cystic neoplasm in the differential diagnosis of every cystic lesion of the pancreas. • Recognize that cystic pancreatic neoplasms are subdivided into four general categories:

Serous cystadenomas (always benign) Mucinous cystic neoplasms (premalignant or malignant) Intraductal papillary mucinous tumors (premalignant or malignant) Other rare cystic tumors (islet cell tumors, papillary tumors) • See table Differential Diagnosis of Acute Pancreatitis. Evidence • Many criteria have been used to distinguish pseudocyst from cystic neoplasms (60; 61; 62; 63; 64; 65). Not one of these criteria is pathognomonic or can establish the diagnosis by itself except positive cytology results for malignancy. • According to a multicenter retrospective study, patients with cystic neoplasm (even if malignant) have excellent prognosis if the lesion is resected (62). Rationale • Approximately 90% of cystic lesions of the pancreas are pseudocysts and only 10% cystic neoplasms. • Every effort must be made to differentiate between a pseudocyst and cystic neoplasm because most neoplasms should be excised, whereas most pseudocysts are treated with observation or drainage. • Despite all efforts it may be very difficult to distinguish with a high degree of certainty between pseudocyst and cystic neoplasm of the pancreas; in general, one should err on the side of resecting a lesion if the exact pathologic type is in question.

Acute Pancreatitis

Top 3. Consultation Consider specialist consultation for diagnostic help in complicated cases of AP. Consider consultation with appropriate specialists in managing selected patients with AP. 3.1 Consider consultation with a gastroenterologist in selected patients with AP. Recommendations • Obtain consultation with a gastroenterologist in the following situations:

Suspected biliary pancreatitis as judged by elevated liver-function test enzymes and evidence seen on ultrasonographic results of gallstones in the gallbladder and dilated bile ducts Recurrent AP of uncertain etiology Unexplained hyperamylasemia in the setting of an atypical clinical picture When specialist procedures, such as ERCP, EUS, sphincter of Oddi manometry, or bile crystal analysis, may be required Evidence • Consensus. Rationale • The diagnosis of biliary pancreatitis may be difficult; patients with alcoholic pancreatitis may have elevation of their liver-function enzymes secondary to alcohol ingestion rather than gallstones. • Ultrasonography may not be able to visualize the gallbladder in some patients because of intestinal gas. • In patients with uncertain etiology of pancreatitis, gastroenterology can assist in establishing the cause. • Some specialized testing, including MRCP, EUS, possibly ERCP, sphincter of Oddi manometry, or bile crystal analysis, may be necessary to establish the presence of occult gallstone pancreatitis, sphincter of Oddi dysfunction, microlithiasis, and pancreas divisum. 3.2 Consider consultation with an interventional radiologist for specialized procedures. Recommendations • Consider consulting an interventional radiologist in patients suspected of having infected pancreatic necrosis to obtain a fine-needle aspiration for Gram stain and culture. Evidence • Pancreatic necrosis develops in approximately 20% of the patients with AP (66). In a longitudinal study of 194 patients with unequivocal AP, pancreatic necrosis developed in 20%. All patients with documented necrosis underwent fine-needle aspiration, and infection was documented in 71% of the patients. Rationale • Interventional radiologists can obtain fine-needle aspirations of pancreatic necrosis and help determine the presence of infection. 3.3 Consider consultation with a gastroenterologist for complex cases of AP or when a procedure may be required. Recommendations

Acute Pancreatitis

• Obtain gastroenterology consultation for patients with:

Potentially severe or complicated AP Suspected biliary pancreatitis who may require ERCP Unexplained AP Idiopathic recurrent AP Endoscopic drainage of pancreatic necrosis, abscesses, and pseudocysts Evidence • Consensus. Rationale • Gastroenterologist expertise is needed for patients with severe pancreatitis judged by the presence of local or systemic complications. • In patients with suspected biliary pancreatitis, ERCP may be needed to diagnose and treat biliary obstruction due to common bile-duct stones. • In patients with unexplained pancreatitis, a thorough evaluation by a specialized consultant is indicated. 3.4 Consider consultation with a surgeon when medical therapy alone is insufficient. Recommendations • Obtain surgical consultation in patients with:

Infected pancreatic necrosis, pancreatic abscess, and pancreatic pseudocyst Biliary pancreatitis for consideration for cholecystectomy Evidence • Minimally invasive approaches vs. open necrosectomy showed significantly reduced complications or death in the treatment of necrotizing pancreatitis, with a risk ratio of 0.57 (157). Rationale • Surgical debridement is indicated in patients with infected pancreatic necrosis, pancreatic abscess, and some cases of persistent pseudocyst resulting from attack of AP. • Cholecystectomy is indicated in patients with biliary pancreatitis. Comments • Endoscopic or percutaneous approaches may be appropriate in conjunction with or in lieu of surgery in selected cases. 3.5 Consider consultation with a critical care physician or pulmonologist. Recommendations • Consider consulting a critical care physician or pulmonologist if arterial hypoxemia develops. Evidence • Consensus. Rationale • Hypoxemia may herald incipient ARDS requiring ventilatory support.

Acute Pancreatitis

Top 4. Hospitalization Hospitalize most patients with AP. 4.1 Hospitalize patients with AP for supportive care and management of complications. Recommendations • Hospitalize most patients with AP for:

Parenteral fluids Pain control Nutritional support Appropriate procedures depending on etiology Monitoring for complications, including hypovolemia, hypoxemia, and infection Evidence • A meta-analysis evaluated the discriminant power of Ranson signs in the prediction of AP severity and outcome compared with clinical judgment (51). Nineteen studies (n=2728) for severity prediction and 10 (n=1513) for prognosis were included. The Ranson signs show a poor predictive power for severity and outcome of AP and did not differ from that of clinical judgment. • Hypoxemia may go unnoticed. The risk is especially high because patients are on narcotics (67). • Adequate pain control can be achieved with parenteral pain medications and patient-controlled analgesia. These require bedside oxygen saturation monitoring, which can be done effectively in the inpatient setting (67). • There is abundant experimental evidence that early aggressive fluid resuscitation and improved delivery of oxygen prevent or minimize pancreatic necrosis and improve survival (68; 69; 70). Rationale • It is impossible to reliably predict the severity of pancreatitis on presentation. • The most commonly used early prognostic signs (Ranson criteria of severity of AP) require evaluating the patient on presentation and then during the initial 48 hours of hospitalization; however, their validity is controversial. • Aggressive intravenous fluid administration is the cornerstone of AP therapy and can only be accomplished in a hospital; it minimizes pancreatic necrosis and improves survival. Comments • Outpatient management may only be appropriate in a patient with acute recurrent pancreatitis if he or she has had multiple attacks in the past and now has a “typical” mild attack of AP. • No trials have compared inpatient vs. outpatient management of patients with AP. • Ranson signs are of most help at the extremes. Many patients have three to five signs, and it is not possible to distinguish the 10% to 20% of patients who will have a fatal outcome from the patients who will not.

Acute Pancreatitis

Top 5. Therapy Provide meticulous supportive care to patients with AP, prescribe fasting for all patients with AP, and consider ERCP in selected cases. 5.1 Provide meticulous supportive care to patients with AP. Recommendations • Provide all patients with AP:

Aggressive intravenous fluids resuscitation Symptomatic medications for pain, nausea, and vomiting Close monitoring for local and systemic complications (see determining the severity of AP) • Recognize that there are no specific drugs for treatment of AP. Evidence • Several drugs have been evaluated by prospective, controlled trials and found ineffective in the treatment of AP. The list, by no means complete, includes glucagon (71; 72; 73; 74), atropine (75), H2 blockers (76; 77; 78), protease inhibitors such as aprotinin and gabexate (79; 80; 81; 82), calcitonin (83), and somatostatin analogues such as octreotide (84; 85; 86; 87). • The latest disappointment is the platelet-activating-factor antagonist lexipafant (88). A randomized, double-blind, placebo-controlled, multicenter trial involving 290 patients showed that lexipafant had no effect on the incidence of organ failure, local complications, or death. Rationale • No specific drug therapy has been shown to alter the course of AP. Comments • In preliminary studies, gabexate and interleukin-10 decreased the incidence of post-ERCP pancreatitis when given before ERCP; however, subsequent trials and meta-analysis have shown marginal, if any, efficacy (89; 90; 91; 92). Neither gabexate nor interleukin-10 is available in the U.S. • Data from a randomized, double-blind trial in 220 patients comparing diclofenac suppository given after ERCP with placebo showed that diclofenac decreased the incidence of post-ERCP pancreatitis (20). The difference in incidence of post-ERCP pancreatitis between the diclofenac group (7 of 110) and the placebo group (17 of 110) barely reached statistical significance (P=0.049). In another double-blind, randomized trial in patients who underwent pancreatography with or without cholangiography, the risk for pancreatitis was significantly lower in the group receiving an indomethacin suppository than in the control group (P=0.01; RR reduction, 88%; adjusted RR, 0.16; NNT=6) (93). • A randomized, controlled trial compared somatostatin, 250 µg iv bolus, given immediately after the diagnostic portion of therapeutic ERCP with placebo. The incidence of post-ERCP pancreatitis was 4.4% in the somatostatin group (n=135) and 13.3% in the placebo group (n=135; P=0.01) (21). • A large (n=1127), randomized, controlled trial found that gabexate and somatostatin were ineffective for the prevention of post-ERCP pancreatitis (22). • A multicenter, placebo-controlled, randomized clinical trial looked at the effect of octreotide administration in the prophylaxis of post-ERCP pancreatitis and hyperamylasemia. The incidence of AP was 2.42% (10 of 414 patients) in the octreotide group and 5.26% (22 of 418 patients) in the control group (P=0.46). The incidence of hyperamylasemia was 12.32% (51 of 414 patients) in the octreotide group and 17.46% (73 of 418 patients) in the control group (P=0.41) (23). 5.2 Institute fasting on presentation in all patients hospitalized with AP.

Acute Pancreatitis

Recommendations • Keep patients NPO until there is clinical improvement. • Recognize that there are no uniform guidelines regarding the proper time to initiate oral feeding. Evidence • The role of fasting as a way to rest the pancreas and promote healing has not been established. It was shown that cholecystokinin-stimulated pancreatic secretion is almost abolished in four different experimental models of AP. This finding probably explains why maneuvers aimed to “rest the pancreas” have failed to show any therapeutic benefit (4). • The decision to reintroduce oral intake is based on sound clinical judgment. The usual criteria used are a decrease or resolution of abdominal pain, a decrease in organ dysfunction (if present), and hunger of the patient. Some authors recommend that elevation of serum amylase/lipase or persistent inflammatory changes seen on CT scan should not discourage the clinician from feeding a hungry asymptomatic patient. Two prospective, nonblinded studies showed that resolution of inflammatory changes on CT scan and elevation of amylase and lipase levels may not take place for several months (94; 95). • A 2011 meta-analysis of 3 randomized, controlled trials comparing liquid and solid diets showed no difference in recurrence of pain (96). • In a multicenter, prospective study from France, longer duration of initial pain, high CT severity index, and serum lipase concentrations greater than three times the upper limit of normal 1 day before refeeding were independently associated with, and increased the risk for, pain relapse (97). Rationale • Most patients with AP cannot tolerate oral intake secondary to abdominal pain, nausea, and vomiting. Comments • In mild AP, refeeding can begin with solid food. • In mild pancreatitis, oral refeeding is generally begun between days 3 and 7 of hospitalization (98). • In a randomized trial, refeeding with a solid meal as the initial meal in mild AP was safe (99). • Oral refeeding may increase abdominal pain (100). 5.3 Consider parenteral or enteral nutrition in some patients with AP. Recommendations • Understand that most patients with mild uncomplicated AP do not benefit from nutritional support. • Consider nutritional support early in the treatment course for patients with moderate to severe disease. • When possible, choose enteral jejunal feeding over TPN as an option for providing exogenous nutrients. • Consider using supplemented TPN in critically ill patients. Evidence • Some retrospective studies suggest that patients with pancreatitis given early TPN are at increased risk for sepsis and pancreatic infection (101; 102; 103). • A prospective study has shown that enteral feeding infused distal to the ligament of Treitz was associated with a decreased rate of complications, including infection, when compared with TPN (104). • In a prospective, randomized trial of TPN vs. jejunal feeding, fifty-three patients with AP who had not improved with conservative therapy after 48 hours were randomly assigned. The durations of feeding and hospital stay were shorter in the jejunal feeding group. Enteral nutrition was also associated with fewer septic (4% vs. 33%) and metabolic (15% vs. 52%) complications, as well as lower cost (savings of $2362). Jejunal feeding, however, met the estimated nutritional needs in only 54% of the patients vs. 88% in the TPN group. The conclusion is that jejunal feeding is safer

Acute Pancreatitis

and less expensive (105). Another randomized, controlled trial confirmed that jejunal nutrition resulted in fewer septic complications and was less expensive than TPN (106). • Evidence-based reviews conclude that enteral feeding reduced mortality, infections, multiple organ failure, and the need for operative interventions compared with TPN and that there was a trend toward reduced hospital length of stay (107; 108). • A meta-analysis of six studies with 263 participants compared enteral nutrition with TPN. Enteral nutrition was associated with a significantly lower incidence of infections (RR, 0.045; P=0.004), reduced surgical interventions to control complications of pancreatitis (RR, 0.48 [CI, 0.22 to 1.00]; P=0.05), and a reduced length of hospital stay (mean reduction, 2.9 days [CI, 1.6 to 4.3 days]; P<0.001) (109). In another randomized, controlled trial, enteral nutrition showed a trend toward faster attenuation of inflammation, with fewer septic complications, and also was a dominant therapy in terms of cost-effectiveness (106). • In a meta-analysis of 5 randomized, controlled trials of enteral vs. parenteral feeding, enteral nutrition resulted in clinically relevant and statistically significant risk reduction for infectious complications, pancreatic infections, and mortality in patients with predicted severe AP (110). • In a randomized, multicenter study in critically ill patients, glutamine-supplemented TPN was associated with a lower incidence of complicated outcome (41% vs. 61%; P<0.05), which was mainly due to a reduced infection rate per patient (mean, 0.45 vs. 0.71; P<0.05) and incidence of pneumonia (10 vs. 19; P<0.05) (111). Rationale • Patients with moderate or severe AP may not be able to receive oral nourishment for a few weeks and need nutritional support. • Enteral nutrition is associated with a lower incidence of infections and a shorter hospital stay than parenteral methods. Comments • Jejunal feeding may be difficult to administer because of difficulty placing and/or displacement of the nasojejunal tube. It appears that nasogastric feeding is equivalent to nasojejunal feeding, but more confirmatory studies are needed (112). • Oral refeeding may increase abdominal pain (100). 5.4 Consider ERCP in the management of patients with acute biliary pancreatitis. Recommendations • Perform ERCP in patients with bile-duct stones seen on ultrasonography, CT, MRCP, or EUS; cholangitis; or severe biliary pancreatitis. • Recognize that ERCP may be of benefit in patients with smoldering pancreatitis or strong suspicion of retained bile-duct stones (judged by persistent elevation of liver-function test results, dilated bile duct, but no direct evidence of ductal stones). • Perform biliary sphincterotomy to relieve biliary obstruction. • Do not perform ERCP in patients with resolved acute biliary pancreatitis before planned elective laparoscopic cholecystectomy. Evidence • A 2012 Cochrane review of five randomized controlled trials of early ERCP vs. conservative management of acute gallstone pancreatitis showed that early ERCP does not affect mortality or complications. However, the studies do support early ERCP for coexisting cholangitis or biliary obstruction (113). • Three published, prospective, randomized trials have examined the role of ERCP vs. conservative management in acute biliary pancreatitis. A study from the United Kingdom found no difference in outcomes in the patients with mild disease, but in patients with severe disease, a significant

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reduction of complications and mortality in the ERCP group was seen when compared with the conservative therapy group (24% vs. 61% in complications and 4% vs. 18% in mortality) (114). • In a prospective, randomized trial, patients with gallstone pancreatitis who underwent endoscopic decompression showed a shorter period of obstruction (P=0.016) and a lower rate of immediate complications (P=0.026) than subjects receiving conservative management. Patients with obstruction lasting 48 hours or less, regardless of the treatment group, had fewer complications than those whose obstruction persisted longer (P<0.001) (115). • A study from Hong Kong found that complications, cholangitis, and death were higher in the conservatively treated group. This effect was more marked in the group with severe pancreatitis (116). • A study from Poland, which has not been published, found a significant reduction of both complications and death in the ERCP/sphincterotomy group as compared with the conservative- management group (17% vs. 36% in complications and 2% vs. 13% in death). The ERCP was particularly beneficial if done within 24 hours. The benefits of sphincterotomy were present in patients with mild as well as severe pancreatitis, although the trend was more pronounced in patients with severe disease (117). • A study from Germany found no benefit from ERCP. Notably, patients with jaundice and cholangitis (probably most likely to benefit from ERCP) were excluded from enrollment (118). • Three of the above four trials (114; 116; 118) were included in a meta-analysis. There was a reduction in complications in patients with predicted severe disease who underwent ERCP compared with those who received conservative therapy. In patients with predicted mild disease, there was no difference in the rate of complications. There was no difference in mortality irrespective of the severity of the disease. • Endoscopic balloon dilation is statistically less successful for stone removal (RR, 0.90 [CI, 0.84 to 0.97]), requires higher rates of mechanical lithotripsy (RR, 1.34 [CI, 1.08 to 1.66]), and carries a higher risk for pancreatitis (RR, 1.96 [CI, 1.34 to 2.89]) (119). • Successful endoscopic drainage of pancreatic necrosis and abscesses has been described in a few series (120; 121; 122). • In a meta-analysis of patients with acute biliary pancreatitis without cholangitis, early ERCP did not significantly reduce the risk for complications of AP (123). Rationale • Although the association is well established, the exact means by which gallstones cause AP is a much debated subject. • All theories revolve around the presence of stones in the common bile duct or their passage via the ampulla of Vater. • By extracting the stones and performing biliary sphincterotomy, one can expect to improve the outcome and prevent further attacks of acute biliary pancreatitis. • Endoscopic biliary sphincterotomy is preferred over balloon dilation to relieve biliary obstruction. 5.5 Base the use of antibiotics on the severity of disease and the presence of proven or suspected infection. Recommendations • Use antibiotics in patients with documented or suspected infection (cholangitis, infected pancreatic necrosis, and infected pseudocyst) and base the choice of antibiotic on bacterial identification and sensitivity testing. • Be aware that prophylactic antibiotics do not reduce infected pancreatic necrosis or mortality in severe necrotic pancreatitis. • Recognize that use of broad-spectrum antibiotic coverage in patients with noninfected pancreatic necrosis with the following possible regimens based on trial evidence is controversial:

Imipenem alone (two trials) Cefuroxime alone (one trial)

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Combination of ceftazidime, amikacin, and metronidazole (one trial) Combination of ofloxacin and metronidazole (one trial) Meropenem • Do not use antibiotics in patients with interstitial (non-necrotizing) pancreatitis. • See table Drug Treatment for Acute Pancreatitis. Evidence • Early studies of prophylactic antibiotics to avoid secondary infection and death had negative results, but the studies included patients with mild disease who are at low risk for infection, and the antibiotics used (ampicillin) have poor penetration in the pancreas (124; 125). • Antibiotics were beneficial in four studies (126), and showed that imipenem significantly reduced pancreatic and nonpancreatic sepsis (P≤0.01) (127); cefuroxime reduced all infectious complications (P<0.01) and deaths (P=0.0284) (128); a regimen of ceftazidime, amikacin, and metronidazole reduced all infectious complications (P<0.03) (129); and protocol use of imipenem significantly reduced pancreatic infection compared with nonprotocol antibiotics (P=0.04) and no antibiotics (P<0.001). • A meta-analysis of controlled trials comparing antibiotic prophylaxis with no prophylaxis in patients with acute necrotizing pancreatitis showed significant reduction in sepsis by 21% (NNT=5) and mortality by 12.3% (NNT=8) (130). There was also a nonsignificant trend toward a decrease in local pancreatic infections. Based on these results, early antibiotic prophylaxis in patients with necrotizing pancreatitis can be suggested, but the best drug and duration of therapy are unknown. • A meta-analysis found a survival advantage for antibiotic therapy (OR, 0.32; P=0.02) and decreased incidence of infected necrosis (OR, 0.51; P=0.04). There was a trend toward increased incidence of fungal infection in the antibiotic therapy group, but it did not reach statistical significance (131). • A double-blind, placebo-controlled trial showed no positive effect on mortality and infected pancreatic necrosis. One hundred fourteen patients with necrotizing AP were randomly assigned to placebo (n=56) or to a combination of ciprofloxacin and metronidazole (n=58) (132). • The role of meropenem is controversial. In a randomized study, meropenem was administered to one group of patients on admission and to a second group only if there was documentation of necrosis. The study showed that early administration of antibiotic was associated with a significant improvement in the prognosis of necrotizing AP because of a reduction in the occurrence of septic complications (133). In another randomized, double-blind, placebo-controlled study, patients with necrotizing pancreatitis were randomly assigned to receive either meropenem or placebo. There were no significant differences between the two groups. Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) of patients in the placebo group (P=0.401). The overall mortality rate was 20% (10 of 50 patients) in the meropenem group vs. 18% (9 of 50 patients) in the placebo group (P=0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of patients in the meropenem and placebo groups, respectively (134). • In a systematic review of 7 studies, there was no statistically significant reduction of mortality (8.4% vs. 14.4%), infected pancreatic necrosis (19.7% vs. 24.4%), nonpancreatic infection (23.7% vs. 36%), or overall infections (37.5% vs. 51.9%) with the use of antibiotics vs. controls. There was a tendency toward reduction of mortality and infected pancreatic necrosis with beta- lactam antibiotic prophylaxis, but this reduction did not reach the level of statistical significance. Imipenem by itself showed no difference in mortality but did show a significant reduction in the rate of infected pancreatic necrosis (P=0.02) (135). • A meta-analysis of randomized, controlled trials was done comparing the use of intravenous antibiotics with placebo or no treatment to reduce infected pancreatic necrosis and mortality in acute necrotizing pancreatitis. The analysis of 7 trials including 467 patients found that prophylactic antibiotics do not reduce infected pancreatic necrosis and mortality (136). • In a multicenter, prospective, double-blind, placebo-controlled, randomized study, 100 patients with clinically severe, confirmed necrotizing pancreatitis received either meropenem (50 patients)

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or placebo (50 patients). No statistically significant difference was found between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention. The study found no support for early prophylactic antimicrobial use to treat severe, acute necrotizing pancreatitis (134). Rationale • In patients with noninfected pancreatic necrosis, antibiotics may decrease the incidence of sepsis, systemic complications (e.g., respiratory failure), and local complications (e.g., infected pancreatic necrosis or pancreatic abscess). • Randomized, prospective trials have shown no benefit from antibiotic use in AP of mild to moderate severity, but antibiotics are clearly indicated in patients with documented infection (cholangitis, infected pseudocyst, infected necrosis). • There is controversy regarding patients with severe pancreatitis and documented necrosis but without documented infection; numerous studies had been conducted with somewhat conflicting results. Comments • Indiscriminate use of prophylactic antibiotics may lead to development of nosocomial infections with resistant pathogens. 5.6 Recognize that nasogastric suction has a limited role in AP. Recommendations • Use nasogastric suction only in patients with severe AP and an ileus. Evidence • Two relatively small prospective, randomized trials have examined the role of nasogastric tube suction in the management of AP (137; 138). In both trials no benefit from nasogastric tube suction was observed. In these studies, stratification of severity was done on clinical grounds rather than CT findings, which precludes us from being able to separate necrotizing from interstitial pancreatitis. Current consensus based on clinical trials suggests a limited use of nasogastric suction (139). Rationale • In the past it was believed that removing acid-dependent stimulation of the pancreas would “rest” the inflamed organ and promote recovery. • Nasogastric suction can relieve symptoms in patients who are vomiting. 5.7 Recognize that surgery has an important role in the management of some patients with AP. Recommendations • Consider surgery in the following circumstances:

Infected pancreatic necrosis and pancreatic abscess Pancreatic pseudocyst Cholecystectomy in patient with biliary AP Evidence • Pancreatic necrosis develops in approximately 20% of patients with AP (66). In a longitudinal study of 194 patients with unequivocal AP, pancreatic necrosis developed in 20%. All patients with documented necrosis underwent fine-needle aspiration, and infection was documented in 71% of the patients. Patients with infected pancreatic necrosis underwent laparotomy and surgical debridement and had a mortality rate of 15% (historical data showed that mortality in this group of patients with conservative management is approximately 50%). There were no deaths in the conservatively treated patient group with noninfected pancreatic necrosis.

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• Most pseudocysts resolve spontaneously (140). Surgery or endoscopic or percutaneous drainage may be indicated for pancreatic pseudocysts that are larger than 6 cm, persist more than 6 weeks after AP, are enlarging in diameter, and are symptomatic. These guidelines are based on a number of retrospective studies (140; 141; 142; 143; 144; 145). • Numerous studies show that once the attack of acute biliary pancreatitis is resolved, there is about a 30% risk for developing a further attack (146; 147; 148; 149; 150; 151; 152; 153). The average time for the second attack in one of the better-documented series was 108 days (146). On the basis of these data, the current recommendation is for the patient to undergo cholecystectomy during the hospitalization period of the index attack after the attack has subsided (154). Rationale • The mortality rate of medically managed infected pancreatic necrosis and pancreatic abscess is >50%. • Some pseudocysts fail to resolve with medical management. • Patients with biliary pancreatitis need cholecystectomy to prevent recurrence of AP attacks. 5.8 Recognize that peritoneal lavage does not have a role in the treatment of severe AP. Recommendations • Be aware that peritoneal lavage, with or without antiprotease, is not recommended. Evidence • In a systematic review, when compared with conservative treatment, peritoneal lavage did not result in a statistically significant difference in the risk for death or complications (155).

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Top 6. Patient Education Instruct patients to follow a regimen that will minimize chances of recurrence of AP or development of chronic pancreatitis. 6.1 After an episode of AP, advise patients about necessary health and lifestyle measures. Recommendations • Depending on the etiology of the initial attack of pancreatitis, instruct patients to avoid identifiable risk factors, such as alcohol, smoking, and certain medications, as well as behaviors that could exacerbate underlying medical conditions, such as elevated triglyceride levels. Evidence • Consensus. • Statin therapy to decrease lipid levels reduces the risk for AP, according to a 2012 meta-analysis of 21 statin trials and 7 fibrate trials. The reduced risk for pancreatitis was statistically significant for statins (P=0.01) but not for the fibrate trials (P=0.053) (156). Rationale • If the patient avoids or controls the precipitating etiologic factor of the attack of pancreatitis, the pancreatitis will not recur.

Acute Pancreatitis

Top 7. Follow-up Follow up to assure the resolution of symptoms and to address underlying etiology. 7.1 Determine whether an episode of AP has completely resolved. Recommendations • Obtain a detailed history and physical examination. Evidence • Consensus. Rationale • The presence or absence of symptoms determines the need for further investigation. 7.2 Tailor specific follow-up in patients with AP to the etiology of the acute episode. Recommendations • In patients with alcoholism, advise abstinence from alcohol or refer for counseling and appropriate treatment. • In patients with high triglyceride levels, control with a combination of dietary regimen and, if indicated, triglyceride-lowering medication (see module Lipid Disorders). • In patients with elevated calcium levels, begin appropriate medical or surgical management to prevent recurrence of hypercalcemia (see module Hypercalcemia). • If a specific drug precipitated the pancreatitis, discontinue its use and substitute another as needed. Evidence • Consensus. Rationale • AP is a self-limited condition that does not recur if the precipitating factor is removed.

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73. Waterworth MW, Barbezat GO, Bank S. Letter: Glucagon in treatment of acute pancreatitis. Lancet. 1974;1:1231. (PMID: 4134700) 74. Dürr HK, Maroske D, Zelder O, Bode JC. Glucagon therapy in acute pancreatitis. Report of a double-blind trial. Gut. 1978;19:175-9. (PMID: 344159) 75. Cameron JL, Mehigan D, Zuidema GD. Evaluation of atropine in acute pancreatitis. Surg Gynecol Obstet. 1979;148:206-8. (PMID: 419422) 76. Broe PJ, Zinner MJ, Cameron JL. A clinical trial of cimetidine in acute pancreatitis. Surg Gynecol Obstet. 1982;154:13-6. (PMID: 6171899) 77. Meshkinpour H, Molinari MD, Gardner L, Berk JE, Hoehler FK. Cimetidine in the treatment of acute alcoholic pancreatitis. A randomized, double-blind study. Gastroenterology. 1979;77:687-90. (PMID: 381092) 78. Hadas N, Wapnick S, Grosberg SJ. Cimetidine in pancreatitis. [Letter] N Engl J Med. 1978;299:487. (PMID: 683286) 79. Trapnell JE, Rigby CC, Talbot CH, Duncan EH. A controlled trial of Trasylol in the treatment of acute pancreatitis. Br J Surg. 1974;61:177-82. (PMID: 4595174) 80. Trapnell JE, Talbot CH, Capper WM. Trasylol in acute pancreatitis. Am J Dig Dis. 1967;12:409-12. (PMID: 5336018) 81. Imrie CW, Benjamin IS, Ferguson JC, McKay AJ, Mackenzie I, O’Neill J, et al. A single-centre double-blind trial of Trasylol therapy in primary acute pancreatitis. Br J Surg. 1978;65:337-41. (PMID: 348250) 82. Büchler M, Malfertheiner P, Uhl W, Schölmerich J, Stöckmann F, Adler G, et al. Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group. Gastroenterology. 1993;104:1165-70. (PMID: 8462805) 83. Goebell H, Ammann R, Herfarth C, Horn J, Hotz J, Knoblauch M, et al. A double-blind trial of synthetic salmon calcitonin in the treatment of acute pancreatitis. Scand J Gastroenterol. 1979;14:881-9. (PMID: 94176) 84. Usadel KH, Leuschner U, Uberla KK. Treatment of acute pancreatitis with somatostatin: a multicenter double blind study. [Letter] N Engl J Med. 1980;303:999-1000. (PMID: 6106160) 85. Choi TK, Mok F, Zhan WH, Fan ST, Lai EC, Wong J. Somatostatin in the treatment of acute pancreatitis: a prospective randomised controlled trial. Gut. 1989;30:223-7. (PMID: 2564834) 86. Bordas JM, Toledo V, Mondelo F, Rodés J. Prevention of pancreatic reactions by bolus somatostatin administration in patients undergoing endoscopic retrograde cholangio-pancreatography and endoscopic sphincterotomy. Horm Res. 1988;29:106-8. (PMID: 2900187) 87. Uhl W, Büchler MW, Malfertheiner P, Beger HG, Adler G, Gaus W. A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis. Gut. 1999;45:97-104. (PMID: 10369711) 88. Johnson CD, Kingsnorth AN, Imrie CW, McMahon MJ, Neoptolemos JP, McKay C, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut. 2001;48:62-9. (PMID: 11115824) 89. Andriulli A, Leandro G, Niro G, Mangia A, Festa V, Gambassi G, et al. Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis. Gastrointest Endosc. 2000;51:1-7. (PMID: 10625786) 90. Devière J, Le Moine O, Van Laethem JL, Eisendrath P, Ghilain A, Severs N, et al. Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography. Gastroenterology. 2001;120:498-505. (PMID: 11159890) 91. Cavallini G, Tittobello A, Frulloni L, Masci E, Mariana A, Di Francesco V. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. Gabexate in digestive endoscopy--Italian Group. N Engl J Med. 1996;335:919-23. (PMID: 8786777) 92. Masci E, Cavallini G, Mariani A, Frulloni L, Testoni PA, Curioni S, et al. Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis. Am J Gastroenterol. 2003;98:2182-6. (PMID: 14572565) 93. Sotoudehmanesh R, Khatibian M, Kolahdoozan S, Ainechi S, Malboosbaf R, Nouraie M. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenterol. 2007;102:978-83. (PMID: 17355281) 94. Lankisch PG, Haseloff M, Becher R. No parallel between the biochemical course of acute pancreatitis and morphologic findings. Pancreas. 1994;9:240-3. (PMID: 8190726) 95. Seidensticker F, Otto J, Lankisch PG. Recovery of the pancreas after acute pancreatitis is not necessarily complete. Int J Pancreatol. 1995;17:225-9. (PMID: 7642969) 96. Meng WB, Li X, Li YM, Zhou WC, Zhu XL. Three initial diets for management of mild acute pancreatitis: a meta-analysis. World J Gastroenterol. 2011;17:4235-41. (PMID: 22072857)

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97. Lévy P, Heresbach D, Pariente EA, Boruchowicz A, Delcenserie R, Millat B, et al. Frequency and risk factors of recurrent pain during refeeding in patients with acute pancreatitis: a multivariate multicentre prospective study of 116 patients. Gut. 1997;40:262-6. (PMID: 9071942) 98. Chebli JM, Gaburri PD, Chebli LA. Oral refeeding in mild acute pancreatitis: an old challenge. World J Gastrointest Pathophysiol. 2011;2:100-2. (PMID: 22180843) 99. Moraes JM, Felga GE, Chebli LA, Franco MB, Gomes CA, Gaburri PD, et al. A full solid diet as the initial meal in mild acute pancreatitis is safe and result in a shorter length of hospitalization: results from a prospective, randomized, controlled, double- blind clinical trial. J Clin Gastroenterol. 2010;44:517-22. (PMID: 20054282) 100. Petrov MS, van Santvoort HC, Besselink MG, Cirkel GA, Brink MA, Gooszen HG. Oral refeeding after onset of acute pancreatitis: a review of literature. Am J Gastroenterol. 2007;102:2079-84; quiz 2085. (PMID: 17573797) 101. Grant JP, James S, Grabowski V, Trexler KM. Total parenteral nutrition in pancreatic disease. Ann Surg. 1984;200:627-31. (PMID: 6435552) 102. Runkel NS, Rodriguez LF, Moody FG. Mechanisms of sepsis in acute pancreatitis in opossums. Am J Surg. 1995;169:227-32. (PMID: 7840385) 103. Medich DS, Lee TK, Melhem MF, Rowe MI, Schraut WH, Lee KK. Pathogenesis of pancreatic sepsis. Am J Surg. 1993;165:46- 50; discussion 51-2. (PMID: 8418702) 104. Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg. 1997;84:1665-9. (PMID: 9448611) 105. Abou-Assi S, Craig K, O’Keefe SJ. Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol. 2002;97:2255-62. (PMID: 12358242) 106. Louie BE, Noseworthy T, Hailey D, Gramlich LM, Jacobs P, Warnock GL. 2004 MacLean-Mueller prize enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment. Can J Surg. 2005;48:298- 306. (PMID: 16149365) 107. Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev. 2010;(1):CD002837. (PMID: 20091534) 108. Petrov MS, Pylypchuk RD, Emelyanov NV. Systematic review: nutritional support in acute pancreatitis. Aliment Pharmacol Ther. 2008;28:704-12. (PMID: 19145726) 109. Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ. 2004;328:1407. (PMID: 15175229) 110. Petrov MS, van Santvoort HC, Besselink MG, van der Heijden GJ, Windsor JA, Gooszen HG. Enteral nutrition and the risk of mortality and infectious complications in patients with severe acute pancreatitis: a meta-analysis of randomized trials. Arch Surg. 2008;143:1111-7. (PMID: 19015471) 111. Déchelotte P, Hasselmann M, Cynober L, Allaouchiche B, Coëffier M, Hecketsweiler B, et al. L-alanyl-L-glutamine dipeptide- supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med. 2006;34:598-604. (PMID: 16505644) 112. Eatock FC, Chong P, Menezes N, Murray L, McKay CJ, Carter CR, et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol. 2005;100:432-9. (PMID: 15667504) 113. Tse F, Yuan Y. Early routine endoscopic retrograde cholangiopancreatography strategy versus early conservative management strategy in acute gallstone pancreatitis. Cochrane Database Syst Rev. 2012;(5):CD009779. (PMID: 22592743) 114. Neoptolemos JP, Carr-Locke DL, London N, Bailey I, Fossard DP. ERCP findings and the role of endoscopic sphincterotomy in acute gallstone pancreatitis. Br J Surg. 1988;75:954-60. (PMID: 3219541) 115. Acosta JM, Katkhouda N, Debian KA, Groshen SG, Tsao-Wei DD, Berne TV. Early ductal decompression versus conservative management for gallstone pancreatitis with ampullary obstruction: a prospective randomized clinical trial. Ann Surg. 2006;243:33-40. (PMID: 16371734) 116. Fan ST, Lai EC, Mok FP, Lo CM, Zheng SS, Wong J. Early treatment of acute biliary pancreatitis by endoscopic papillotomy. N Engl J Med. 1993;328:228-32. (PMID: 8418402) 117. Nowak A, Nowakowska-Dulawa E, Marek T, Rybicka J. Final results of the prospective, randomized controlled study of endoscopic sphincterotomy versus conventional management in acute biliary pancreatitis [Abstract]. Gastroenterology. 1995;108(Suppl):A380. 118. Fölsch UR, Nitsche R, Lüdtke R, Hilgers RA, Creutzfeldt W. Early ERCP and papillotomy compared with conservative treatment for acute biliary pancreatitis. The German Study Group on Acute Biliary Pancreatitis. N Engl J Med. 1997;336:237-42. (PMID: 8995085)

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119. Weinberg BM, Shindy W, Lo S. Endoscopic balloon sphincter dilation (sphincteroplasty) versus sphincterotomy for common bile duct stones. Cochrane Database Syst Rev. 2006:CD004890. (PMID: 17054222) 120. Papachristou GI, Takahashi N, Chahal P, Sarr MG, Baron TH. Peroral endoscopic drainage/debridement of walled-off pancreatic necrosis. Ann Surg. 2007;245:943-51. (PMID: 17522520) 121. Seewald S, Groth S, Omar S, Imazu H, Seitz U, de Weerth A, et al. Aggressive endoscopic therapy for pancreatic necrosis and pancreatic abscess: a new safe and effective treatment algorithm (videos). Gastrointest Endosc. 2005;62:92-100. (PMID: 15990825) 122. Hookey LC, Debroux S, Delhaye M, Arvanitakis M, Le Moine O, Devière J. Endoscopic drainage of pancreatic-fluid collections in 116 patients: a comparison of etiologies, drainage techniques, and outcomes. Gastrointest Endosc. 2006;63:635-43. (PMID: 16564865) 123. Petrov MS, van Santvoort HC, Besselink MG, van der Heijden GJ, van Erpecum KJ, Gooszen HG. Early endoscopic retrograde cholangiopancreatography versus conservative management in acute biliary pancreatitis without cholangitis: a meta-analysis of randomized trials. Ann Surg. 2008;247:250-7. (PMID: 18216529) 124. Finch WT, Sawyers JL, Schenker S. A prospective study to determine the efficacy of antibiotics in acute pancreatitis. Ann Surg. 1976;183:667-71. (PMID: 788655) 125. Craig RM, Dordal E, Myles L. Letter: The use of ampicillin in acute pancreatitis. Ann Intern Med. 1975;83:831-2. (PMID: 1106281) 126. Kramer KM, Levy H. Prophylactic antibiotics for severe acute pancreatitis: the beginning of an era. Pharmacotherapy. 1999;19:592-602. (PMID: 10331822) 127. Pederzoli P, Bassi C, Vesentini S, Campedelli A. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet. 1993;176:480-3. (PMID: 8480272) 128. Sainio V, Kemppainen E, Puolakkainen P, Taavitsainen M, Kivisaari L, Valtonen V, et al. Early antibiotic treatment in acute necrotising pancreatitis. Lancet. 1995;346:663-7. (PMID: 7658819) 129. Delcenserie R, Yzet T, Ducroix JP. Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis. Pancreas. 1996;13:198-201. (PMID: 8829189) 130. Sharma VK, Howden CW. Prophylactic antibiotic administration reduces sepsis and mortality in acute necrotizing pancreatitis: a meta-analysis. Pancreas. 2001;22:28-31. (PMID: 11138967) 131. Bassi C, Larvin M, Villatoro E. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2003:CD002941. (PMID: 14583957) 132. Isenmann R, Rünzi M, Kron M, Kahl S, Kraus D, Jung N, et al. Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial. Gastroenterology. 2004;126:997-1004. (PMID: 15057739) 133. Manes G, Uomo I, Menchise A, Rabitti PG, Ferrara EC, Uomo G. Timing of antibiotic prophylaxis in acute pancreatitis: a controlled randomized study with meropenem. Am J Gastroenterol. 2006;101:1348-53. (PMID: 16771960) 134. Dellinger EP, Tellado JM, Soto NE, Ashley SW, Barie PS, Dugernier T, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study. Ann Surg. 2007;245:674-83. (PMID: 17457158) 135. Villatoro E, Mulla M, Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2010;(5):CD002941. (PMID: 20464721) 136. Bai Y, Gao J, Zou DW, Li ZS. Prophylactic antibiotics cannot reduce infected pancreatic necrosis and mortality in acute necrotizing pancreatitis: evidence from a meta-analysis of randomized controlled trials. Am J Gastroenterol. 2008;103:104-10. (PMID: 17925000) 137. Naeije R, Salingret E, Clumeck N, De Troyer A, Devis G. Is nasogastric suction necessary in acute pancreatitis? Br Med J. 1978;2:659-60. (PMID: 698650) 138. Loiudice TA, Lang J, Mehta H, Banta L. Treatment of acute alcoholic pancreatitis: the roles of cimetidine and nasogastric suction. Am J Gastroenterol. 1984;79:553-8. (PMID: 6377878) 139. Reynaert MS, Dugernier T, Kestens PJ. Current therapeutic strategies in severe acute pancreatitis. Intensive Care Med. 1990;16:352-62. (PMID: 2246416) 140. Bradley EL, Clements JL Jr, Gonzalez AC. The natural history of pancreatic pseudocysts: a unified concept of management. Am J Surg. 1979;137:135-41. (PMID: 758840) 141. Yeo CJ, Bastidas JA, Lynch-Nyhan A, Fishman EK, Zinner MJ, Cameron JL. The natural history of pancreatic pseudocysts documented by computed tomography. Surg Gynecol Obstet. 1990;170:411-7. (PMID: 2326721) 142. O’Malley VP, Cannon JP, Postier RG. Pancreatic pseudocysts: cause, therapy, and results. Am J Surg. 1985;150:680-2. (PMID: 3907380)

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Top Glossary AP acute pancreatitis APACHE Acute Physiology and Chronic Health Evaluation ARDS acute respiratory distress syndrome AST aspartate aminotransferase BISAP Bedside Index for Severity in Acute Pancreatitis BMI body mass index BUN blood urea nitrogen CBC complete blood count CNS central nervous system CT computed tomography DIC disseminated intravascular coagulation ERCP endoscopic retrograde cholangiopancreatography EUS endoscopic ultrasonography GI gastrointestinal

H2 histamine-2 Hct hematocrit iv intravenous LDH lactic dehydrogenase MRCP magnetic resonance cholangiopancreatography MRI magnetic resonance imaging NNT number needed to treat NPO nothing by mouth

Acute Pancreatitis

PaO2 arterial partial pressure of oxygen prn as needed PT prothrombin time PTT partial thromboplastin time RR relative risk TPN total parenteral nutrition

Terms

Cullen sign Ecchymosis around the umbilicus Grey-Turner sign Local skin discoloration of loin and umbilicus due to acute hemorrhagic pancreatitis

Acute Pancreatitis

Top Tables

Laboratory and Other Studies for Acute Pancreatitis

Test Sensitivity (%) Specificity (%) Notes

Serum amylase levels (cutoff values just above 90% 70% All studies to date that address the role of normal range) amylase and lipase in diagnosing AP suffer from insufficient diagnostic gold standard

Serum amylase levels (cutoff values three times 60% 99% All studies to date that address the role of the upper limit of normal) amylase and lipase in diagnosing AP suffer from insufficient diagnostic gold standard

Serum lipase levels (cutoff values three times the 90%-100% 99% All studies to date that address the role of upper limit of normal) amylase and lipase in diagnosing AP suffer from insufficient diagnostic gold standard

CBC Check in all patients with suspected AP

Liver function test Check in all patients with diagnosed AP. Elevated liver-function test results raise the suspicion for biliary pancreatitis

Triglyceride level Check in all patients with diagnosed AP of unclear etiology because hypertriglyceridemia can be the underlying etiology of AP

Electrolyte levels Check in all patients. Frequent monitoring and adjustments are needed

Calcium level Calcium levels can decrease and are negative prognostic factor

BUN and creatinine levels The incidence of renal insufficiency is 4%, 22%, and 45% in patients with interstitial, noninfected necrosis, and infected necrosis AP, respectively

Glucose level Glucose levels can increase and are negative prognostic factors

PT/PTT May be elevated in AP

Abdominal and chest radiographs Can exclude other processes that can cause acute abdominal pain, such as perforated viscus or obstructed bowel

Abdominal ultrasonography Excellent test to evaluate for presence of gallstones

CT or MRI The test of choice to determine the presence of local complications

Test for arterial hypoxemia Pulse oximetry in mild cases of AP and arterial blood gas in severe cases of AP

Acute Pancreatitis

AP = acute pancreatitis; BUN = blood urea nitrogen; CBC = complete blood count; CT = computed tomography; MRI = magnetic resonance imaging; PT = prothrombin time; PTT = partial thromboplastin time.

Acute Pancreatitis

Differential Diagnosis of Acute Pancreatitis

Disease Characteristics

Acute pancreatitis Epigastric or diffuse abdominal pain that is constant; radiates to back, occasionally improves with sitting or leaning forward Review history carefully for potential etiologic factors

Perforated viscus, especially peptic ulcer Very sudden onset Intraperitoneal air present In AP, the pain gradually increases over 30 minutes to 1 hour

Acute cholecystitis and biliary colic Pain tends to be located in the epigastrium and right upper quadrant and radiates to the right shoulder or shoulder blade. Liver-function test results are frequently elevated. Ultrasonography may show thickened gallbladder, pericholecystic fluid In AP, the pain tends to radiate to the back. Liver-function test results can be elevated in biliary AP

Intestinal obstruction Pain is colicky. Obstructive pattern is seen on imaging study (CT or abdominal series) In AP, the pain is constant. Paralytic ileus pattern can be seen on imaging

Mesenteric vascular occlusion Usually there is a discrepancy between the symptoms (severe pain) and physical examination (fairly benign abdominal exam). The classic triad for mesenteric ischemia is postprandial abdominal pain, weight loss, and abdominal bruit In AP, the symptoms and physical exam correlate (severe pain is associated with marked tenderness and guarding on physical exam)

Dissecting aortic aneurysm Sudden onset. Pain may radiate to the lower extremity and/or back In AP, the pain does not radiate to the lower extremity and is not associated with a pulsatile mass

Renal colic Pain is localized in the flank and radiates to the genital area. Dysuria may be present. Urinalysis shows active sediment Urinalysis is unremarkable

Myocardial infarction Electrocardiogram is usually abnormal Myocardial infarction should be in the differential diagnosis in all patients with upper abdominal pain

Connective tissue disorders with vasculitis Other signs of vasculitis are usually present (skin, joint, eye, and kidney involvement) AP can be due to vasculitis

Appendicitis The pain may start in the epigastrium but eventually migrates to the right lower quadrant Ultrasonography and CT are very helpful in the diagnosis of appendicitis

Ectopic pregnancy Sudden onset pain. Menstrual abnormalities usually precede the onset of the pain Rapidly decreasing hematocrit and intraperitoneal pelvic fluid on imaging should raise the suspicion for ectopic pregnancy

Pneumonia Fever, malaise, and other respiratory symptoms (dyspnea, cough, sputum production, chest pain) are usually present Changes on chest physical exam and abnormalities on chest x-ray film can be seen in AP. This can be due to ARDS or pleural effusion

Diabetic ketoacidosis Blood glucose is always elevated

Acute Pancreatitis

Blood glucose may be elevated in severe AP but usually develops later in the clinical course

Familial Mediterranean fever Family history of recurrent attacks of fever associated with peritonitis, pleuritis, and arthritis is present. Familial Mediterranean fever is more common in Armenian and Sephardic Jews Fever is almost always present in familial Mediterranean fever

AP = acute pancreatitis; ARDS = acute respiratory distress syndrome; CT = computed tomography.

Acute Pancreatitis

Drug Treatment for Acute Pancreatitis

Drug or Drug Class Dosing Side Effects Precautions Clinical Use

Antibiotics Use in patients with documented or suspected infection

Imipenem/cilastatin (Primaxin) 500 mg IV q8hr Nausea, vomiting diarrhea, injection If CrCl<70 or weight<70 kg, decrease site reactions dose. Caution with seizure disorder

Cefuroxime (Ceftin) 1.5 g IV q8hr Hematologic adverse reactions, If CrCl<20, decrease dose hypersensitivity reactions, increased BUN and SCr, elevated hepatic enzymes, diarrhea nausea, vomiting

Ceftazidime (Fortaz, Tazicef) 1 g IV q8hr Hematologic adverse reactions, If CrCl<50, decrease dose Used with amikacin and metronidazole hypersensitivity reactions, increased BUN and SCr, elevated hepatic enzymes, diarrhea

Amikacin Individualize dosing Neurotoxicity, ototoxicity, Used with ceftazidime and nephrotoxicity, neuromuscular metronidazole blockade, respiratory paralysis. Dosing is highly variable; serum levels should guide dosing. Avoid with pregnancy. Caution with severe hepatic disease. Decrease dose with CKD

Metronidazole (Flagyl, Metro) 500 mg IV q12hr GI side effects, neurotoxicity, phlebitis Carcinogenicity. Avoid with Used with amikacin and ceftazidime pregnancy. Avoid alcohol. Decrease dose by 50% with severe hepatic disease. Caution with: CKD, warfarin

Pain medications

Opioids Respiratory and CNS depression, Caution with GI motility disorders hypotension, nausea, vomiting, constipation, biliary spasm, pruritus, urinary retention, CV adverse reactions, tolerance

Fentanyl transdermal (Duragesic) Patients must be opioid tolerant. Start Application site reactions (Transdermal): High concentration Titrate to adequate pain control and no with 25 mcg/ hour opioid for opioid tolerant patients only, respiratory depression hypoventilation risk, interacts with CYP3A4 inhibitors, avoid heat sources, abuse potential. Use lowest possible dose with hepatic disease or CKD. Remove patch before MRI

Hydromorphone (Dilaudid) 1-4 mg IV q3-4hr prn Respiratory depression, potential for Titrate to adequate pain control and no abuse and medication errors, drug respiratory depression interactions with other CNS depressants and alcohol. Decrease initial dose with: moderate or severe hepatic disease, CrCl<60

Meperidine (Demerol) 50-150 mg SC, IV or IM q3-4hr prn Less biliary spasm than morphine Caution with: hepatic disease, CKD, Titrate to adequate pain control with no

Acute Pancreatitis

elderly due to accumulation of respiratory depression neurotoxic metabolite. Caution with seizure disorder

= black box warning; bid = twice daily; BUN = blood urea nitrogen; CKD = chronic kidney disease; CNS = central nervous system; CrCl = creatinine clearance; CV = cardiovascular; GI = gastrointestinal; IM = intramuscular; IV = intravenous; MRI = magnetic resonance imaging; PO = oral; prn = as needed; q12hr = every 12 hours; q3-4hr = every 3 to 4 hours; qd = once daily; qid = four times daily; SC = subcutaneous; SCr = serum creatinine; tid = three times daily PIER provides key prescribing information for practitioners but is not intended to be a source of comprehensive drug information.

Acute Pancreatitis

Medications Associated with Acute Pancreatitis

Strong Association Weak Association Relationship Uncertain

Asparaginase Corticosteroids MethyldopaEstrogens (related to dose and generation of hyperlipidemia)

Thiazide diuretics Pentamidine OctreotideValproic Acid

5-Aminosalicylic acidAzathioprine Angiotensin-converting enzyme inhibitors Incretin mimetic drugs

Tetracycline CyclosporineSulfonamides Zalcitabine, stavudine

Cimetidine6-Mercaptopurine Acetaminophen

Furosemide ErythromycinDidanosine

Metronidazole

Acute Pancreatitis

Etiology of Acute Pancreatitis

Alcohol

Biliary stones

Drugs

Hyperlipidemia

Hypercalcemia

Hereditary

Sphincter of Oddi dysfunction

Microlithiasis

Pancreas divisum

Vasculitis

ERCP

Trauma

Postsurgical

Cystic fibrosis

Pancreatic cancer

Cystic lesions of the pancreas

Intraductal papillary mucinous tumors

Cystic fibrosis

Tropical pancreatitis

Viral or parasitic infections

Penetrating peptic ulcer

Idiopathic

ERCP = endoscopic retrograde cholangiopancreatography.

Acute Pancreatitis

Causes of Increased Amylase

Pancreatic diseases

Acute pancreatitis

Pancreatic cancer

Chronic pancreatitis

Other serious intra-abdominal diseases

Acute cholecystitis

Common bile-duct obstruction

Perforation of esophagus, stomach, small bowel, or colon

Intestinal ischemia

Intestinal obstruction

Acute appendicitis

Ruptured ectopic pregnancy

Diseases of salivary glands

Mumps

Scorpion sting

Effects of alcohol

Tumors

Ovarian cyst

Carcinoma of the lung

Renal insufficiency

Miscellaneous

Anorexia nervosa

Macroamylasemia

Head trauma

Diabetic ketoacidosis

Human immunodeficiency virus

Acute Pancreatitis

Ranson's Criteria

At admission During initial 48 hours

Age >55 years Hct decrease of 10 vol %

Leukocyte count >16,000/mm3 BUN increase of >5 mg/dL

Glucose >200 mg/dL Ca <8 mg/dL

LDH >350 U/L PaO2 <60 mm Hg

AST >250 U/L Base deficit >4 mEq/L

Fluid sequestration >6 L

AST = aspartate aminotransferase; BUN = blood urea nitrogen; Ca = calcium; Hct = hematocrit; LDH = lactic dehydrogenase; PaO2 = arterial partial pressure of oxygen.

Acute Pancreatitis

Top Figures

Pancreatic Necrosis CT scan demonstrating walled-off pancreatic necrosis (arrows) virtually replacing the entire pancreatic body and tail.

Acute Pancreatitis

Acute Interstitial Pancreatitis CT scan of a patient with acute interstitial pancreatitis showing enlargement of the gland, with contour irregularities, inhomogeneous attenuation and peripancreatic edema.

Acute Pancreatitis

Acute and Chronic Pancreatitis CT scan of a patient with chronic pancreatitis as documented by the pancreatic calcifications and acute pancreatitis indicated by the gland's contour irregularities and inhomogeneous attenuation.

Acute Pancreatitis

Autoimmune Pancreatitis CT scan demonstrating autoimmune pancreatitis with the classic enlarged and "sausage-shaped" pancreas (arrows).